Leading the Charge in Cure Research

by Jeffrey Laurence, M.D.

Published Thursday, March 15, 2012

The search for a cure has
been the top priority of amfAR’s research program for more than a decade,
bolstered by numerous cycles of targeted grants and fellowship awards as well as
the recent collaborative work of the amfAR Research Consortium on HIV
Eradication (ARCHE). A critical barrier to curing AIDS is the persistence of
reservoirs of latently infected cells. People with HIV who are successfully
treated with antiretroviral drugs (ARV) still have infected cells in which HIV
remains silent, invulnerable to attack by the immune system or standard anti-HIV
drugs. Strategies to destroy these latent reservoirs─including enhanced immune
attack and a “shock and kill” approach─are active areas of our grantees’
research.

In the March issue of the
journal Cell Stem
Cell, three current and former
ARCHE grantees, Dr. Keith Jerome from the Fred Hutchinson Cancer Research Center
in Seattle and Drs. Steven Deeks and Joseph McCune from the University of
California-San Francisco, acknowledge “the amfAR Eradication Program for its
contributions in moving the cure agenda forward.” The authors─who met and first
discussed the idea for their paper at a stem cell think tank organized by
amfAR in September 2011─suggest
that one might be able to create an HIV-resistant immune system in an infected
person by genetically engineering a person’s own stem cells. This strategy is
based on the one successful “proof of concept” that AIDS can be cured: the
“Berlin patient.” The authors admit that such “gene modification of stem cells
will be an expensive intervention” but suggest that “it may prove to be
cost-effective given that decades-long administration of antiretroviral therapy
would cost several hundred thousand dollars per person.”

Working on the “shock and
kill” approach, another ARCHE member, Dr. Robert Siliciano of Johns Hopkins
University, describes his newest findings in the March issue of the Journal of Antimicrobial
Chemotherapy. The “shock and kill”
approach involves awakening latent virus and then killing it with ARVs, enhanced
immune attack, or a combination of these methods. Using a model for latently
infected T cells that they developed, Dr. Siliciano and colleagues tested a
large number of chemical compounds—a “library”—to see which, if any, might
activate growth of HIV without causing harm. They discovered two types of
chemicals that not only could awaken HIV but did so without broadly stimulating
the cells to produce potentially harmful immune hormones (cytokines). Supporting
the possibility of turning such chemicals into useful drugs was the fact that
they had characteristics of known drugs that are readily absorbed by the body
and taken up by cells.

These contributions and the
work of many other amfAR grantees were shared at the prestigious 19th annual Conference on Retroviruses and
Opportunistic Infections (CROI) in Seattle March 5−8. More than 25 oral and
poster presentations on the results of amfAR-funded research were
given─including major oral presentations addressing AIDS cure strategies given
by Sharon Lewin, Maria Buzón, Adam Spivak, Liang Shan, Sifei Xing, and Anthony
Cillo─making it clear that amfAR is leading the charge in cure
research.